Exploring the boron chemical space towards new BNCT agents

Boron Neutron Capture Therapy (BNCT) is a binary therapy that employs neutron irradiation on the boron agents to release high-energy helium and alpha particles able to kill cancer cells. This technique is used for cancer treatment by a selective accumulation of 10B-containing compounds in tumor cells and is limited to tumors not responding to conventional therapies, such as glioblastoma multiforme, melanoma, and head, and neck tumors. Optimal response to BNCT depends critically on the maximal 10B accumulation in tumor cells when performing the neutron irradiation. Until recently, the use of nuclear reactors as a primary source of neutrons has limited BNCT application in a hospital setting. Moreover, the only two compounds clinically used, boronophenylalanine (BPA) and sodium borocaptate (BSH), have shown significant limitations. The development of accelerators as neutron sources has sparked new interest in BNCT, stimulating the research towards the design of new boronated molecules. We herein present the synthesis of new compounds containing boron moieties linked to saccharidic structures as potential agents for BNCT. We will focalize on the development of new theranostic agents containing a trifluoroborate moiety that can furnish at the same time the boron atom required for BNCT, while the fluorine atoms can be exchanged by an 18F isotope which can be exploited as a positron emitter, guiding BNCT in an orthogonal modality. Fluorine 18 is a radiotracer commonly used for Positron Emission Tomography (PET) that permits the tracking of compounds in vivo, allowing the visualization of the compound biodistribution in the body and its accumulation in the tumor. To ensure a higher tumor affinity vs normal cells, trifluoroborate will be conjugated to molecules able to selectively target cancer cells. In our compounds, sugars represent the substructures of choice exploiting their higher consumption by malignant cells and their selective uptake thanks to GLUT transporters.


Daniela Imperio

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